A pervasive aspect of Autism Spectrum Disorder (ASD) is hypersensitivity to visual stimuli. This sensitivity may be due to hyperexcitability in neural circuits, consistent with the high rates of epilepsy and abnormal EEG in ASD. Some researchers have proposed that this hyperexcitability may be related to imbalances between excitation and inhibition. These ideas, while potentially groundbreaking, have for the most part remained relatively vague. This proposal will test concrete versions of these ideas using psychophysical experiments and precise computational models that can distinguish between changes in excitation strength, inhibition strength, time constants, and several other key parameters of neural dynamics. This approach will be used to identify mistuned computational parameters in ASD (if any), thus providing a critical constraint on possible biophysical mechanisms underlying atypical perception in ASD. Mistuned parameters observed in the visual system may reflect a broader core computational deficit in the ASD brain, providing a foundation not only for sensory disruptions, but also for the cognitive and social differences. Aim 1 (Empirical) will investigate the cortical dynamics in ASD using binocular rivalry, a particularly well-studied visual phenomenon for which there are precise computational models that rely on a balance of excitation and inhibition. Preliminary empirical results have revealed a large and significant difference between ASD and control populations in the duration of mixed percepts reported during binocular rivalry. Preliminary theoretical results, using a firing rate model, have identified three possible parameter mistunings that explain the difference; the proposed research is designed to support or refute each of these hypotheses. Aim 2 (Theory) will explore the dynamics of this firing rate model and two other models, to understand how the disruptions underlying abnormal binocular rivalry might relate to the hyperexcitability observed in ASD. One of these models will be selected to serve as a general platform for understanding, and making predictions about, cortical dynamics in ASD. The training component of this fellowship will include (a) immersion in ASD research and the opportunity to work directly with ASD participants; (b) rigorous training in psychophysics and computational modeling. The proposed project is fully in line with the NIMH mission. It investigates how neural circuits interact to contribute to observable behaviors in a patient population (Strategy 1.1), and it develops behavioral indicators associated with mental disorders (Strategy 1.3). PUBLIC HEALTH RELEVANCE: This project will investigate atypical visual perception in autism in order to understand the neural mechanisms that underlie this disorder. Understanding precisely how the autistic brain is different from the non-autistic brain is a critical step toward developing effective treatments or cures.